title: Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responses.
abstract: BACKGROUND
  Psoriasis is a chronic inflammatory skin disease that is considered to result from activated T cells stimulated by a population of inflammatory dermal dendritic cells (DCs). The origin and identity of these inflammatory dermal DCs are largely unknown.
  
  
  OBJECTIVE
  We previously identified slanDCs (6-sulfo LacNAc) DCs as a rich source of TNF-α and as the early major source of IL-12. Here we studied the relevance of slanDCs as inflammatory dermal DCs in psoriasis.
  
  
  METHODS
  Psoriasis skin samples were stained for the presence of activated slanDCs. Functional studies were carried out to determine the cytokine production of slanDCs, their T(h)17/T(h)1 T-cell programming, and their migration behavior.
  
  
  RESULTS
  Large numbers of IL-23, TNF-α, and inducible nitric oxide synthase expressing slanDCs were found in psoriatic skin samples, which can be recruited by C5a, CX3CL1, and CXCL12. SlanDCs isolated from blood produced high levels of IL-1ß, IL-23, IL-12, and IL-6. Compared with classic CD1c(+) DCs, slanDCs were far more powerful in programming T(h)17/T(h)1 T cells that secrete IL-17, IL-22, TNF-α, and IFN-γ, yet CD1c(+) DCs induced a higher IL-10 production of T cells. Self-nucleic acids complexed to cathelicidin LL37 trigger endosomal Toll-like receptor (TLR) signaling (TLR7, TLR8, TLR9) and are key factors for the activation of DCs in psoriasis. We show that slanDCs respond particularly well to complexes formed of self-RNA and LL37. Similarly, slanDCs stimulated with a synthetic TLR7/8 ligand produced high levels of proinflammatory cytokines.
  
  
  CONCLUSIONS
  Our study defines slanDCs as inflammatory dermal DCs in psoriasis and identifies their strong capacity to induce T(h)17/T(h)1 responses.
authors.affiliation: Faculty of Medicine, Institute of Immunology, Technical University of Dresden, Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Hänsel
authors.forename: Claudia
authors.initials: C
authors.lastname: Günther
authors.forename: Jens
authors.initials: J
authors.lastname: Ingwersen
authors.forename: Josephine
authors.initials: J
authors.lastname: Starke
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Michael
authors.initials: M
authors.lastname: Bachmann
authors.forename: Michael
authors.initials: M
authors.lastname: Meurer
authors.forename: Ernst Peter
authors.initials: EP
authors.lastname: Rieber
authors.forename: Knut
authors.initials: K
authors.lastname: Schäkel
mesh_terms: D000328:Adult; D000368:Aged; D000606:Amino Sugars / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C467438:6-sulfo-LacNac; D000606:Amino Sugars